Neonatal and early life immune responses to various forms of vaccine antigens qualitatively differ from adult responses: predominance of a Th2‐biased pattern which persists after adult boosting

Abstract

Induction of neonatal immune responses to vaccine antigens is believed to be of limited efficacy because of immune immaturity and particular susceptibility to tolerogenic signals during this period of life. To characterize particular features of neonatal immune responses to vaccine antigens, we assessed the capacity of BALB/c mice at different stages of immunological maturation to respond to a selection of vaccine antigens and presentation systems. Significant B and T cell responses to vaccine antigens (tetanus and measles virus peptides, tetanus toxoid, live viral attenuated measles virus, canarypox recombinant measles vector or bacillus Calmette-Guérin) were obtained as early as the first week of life. However, these neonatal responses differed qualitatively from adult responses by a decreased IgG2a/IgG1 ratio of vaccine-specific antibodies, the secretion of significantly higher interleukin-5 and lower interferon-gamma levels by vaccine-specific T cells and an impaired induction of cytotoxic T cell precursors. This pattern of biased Th2 versus Th1 responses induced upon early exposure to vaccines was not reversed by decreasing the doses of vaccine antigens. It did not disappear with aging and was still reflected in adult responses to booster immunization with the corresponding antigen. Thus, neonatal immunization can induce significant vaccine specific responses with a predominance of a Th2 pattern which can persist in boosted adult mice.

Genetic regulation of immune responses to vaccines in early life

“…Early immunization is required to impact on this mortality, but the development of vaccines that are effective at birth is impeded by the immaturity of the immune system. [3][4][5] The antibody (Ab) responses to T-cell-independent and many T-celldependent vaccine antigens are lower in young infants when compared to older children or adults. [6][7][8][9][10] Qualitative differences in Ab responses in infants include reduced Ab avidity and repertoire, and different immunoglobulin G (IgG) subclass distribution.…”

Early life T cell responses to pneumococcal conjugates increase with age and determine the polysaccharide‐specific antibody response and protective efficacy

“…However, it has been demonstrated that significant IgG responses may be induced after immunization with protein antigens (reviewed in [23]), indicating that T cell help to promote isotype switch of B cells from IgM to IgG is present already in the neonatal period of life. The IgG subclass pattern observed after early life immunization of mice is, nevertheless, characterized by a relatively high IgG1/IgG2a ratio [29,30]. This pattern reflects the Th2-biased conditions of the immune system in the newborn, shown by low production of IFN-c, but relatively high production of IL-4, IL-5 and IL-13 after immunization with TD antigens under neutral conditions [30][31][32][33].…”

“…The IgG subclass pattern observed after early life immunization of mice is, nevertheless, characterized by a relatively high IgG1/IgG2a ratio [29,30]. This pattern reflects the Th2-biased conditions of the immune system in the newborn, shown by low production of IFN-c, but relatively high production of IL-4, IL-5 and IL-13 after immunization with TD antigens under neutral conditions [30][31][32][33].…”

Neonatal Administration of IL-12 Enhances the Protective Efficacy of Antiviral Vaccines

“…Forsthuber et al (8) demonstrated that injection of neonatal animals with protein Ags in IFA actually induces immune deviation rather than tolerance and stimulates preferential expression of Th cell type 2 (Th2) cytokines and Ab isotypes. Similarly, Siegriest and colleagues (9,10) found that neonatal vaccine immunization results in biased Th2-type responses that still remain after adult boosting. Collectively, these findings have significant implications for neonatal vaccination strategies and suggest that redirection of the neonatal immune system to a Th1 pathway might increase responsiveness to vaccine Ags.…”